The main objective of the proposed research is the development of chemical methods for selective modification and cleavage of proteins, and the use of such methods for gaining information regarding the structure and function of proteins and enzymes. Specific methods for chemical cleavage of proteins at cysteine, tryptophan, proline and selected methionine residues, that are of considerable potential utility in primary structure determination, will be developed and improved. Novel methods for selective oxidation of methionine residues will be developed and used for probing tertiary structures of proteins, and for studying the role of methionine residues in the biological activity of proteins. The use of S-cyanylation as a specific probe for evaluating the type and extent of involvement of thiol groups in enzymic catalysis will be explored. The mode of action of enzymes which recognize or react with Beta-lactam drugs of the penicillin and the penicillin and the cephalosporin types will be studied using various methods of chemical modification. BIBLIOGRAPHIC REFERENCES: Y. Shechter, Y. Burstein and A. Patchornik, Selective oxidation of methionine residues in proteins. Biochemistry, 14, 4497 (1975). Y. Shechter, Y. Burstein and A. Patchornik, Oxidation of methionine residues in proteins. Israel J. Med. Sci., 11, 1171 (1975).